Variant chr19-18257723-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001145304.2(IQCN):c.3561C>A(p.His1187Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,610,372 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00059 ( 2 hom., cov: 33)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

IQCN
NM_001145304.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.347

Variant links:

Genes affected

IQCN (HGNC:29350): (IQ motif containing N) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

IQCN links:

IQCN (HGNC:):

IQCN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010547638).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQCN	NM_001145304.2 linkuse as main transcript	c.3561C>A	p.His1187Gln	missense_variant	4/4	ENST00000392413.5	NP_001138776.1	Q9H0B3-4
IQCN	NM_025249.4 linkuse as main transcript	c.3000C>A	p.His1000Gln	missense_variant	4/4		NP_079525.1	Q9H0B3-1
IQCN	NM_001145305.2 linkuse as main transcript	c.2862C>A	p.His954Gln	missense_variant	4/4		NP_001138777.1	Q9H0B3-5A0JP07
IQCN	XM_005260084.2 linkuse as main transcript	c.3561C>A	p.His1187Gln	missense_variant	4/4		XP_005260141.1	Q9H0B3-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IQCN	ENST00000392413.5 linkuse as main transcript	c.3561C>A	p.His1187Gln	missense_variant	4/4	1	NM_001145304.2	ENSP00000376213.2	Q9H0B3-4
IQCN	ENST00000600328.7 linkuse as main transcript	c.3000C>A	p.His1000Gln	missense_variant	4/4	1		ENSP00000470780.1	Q9H0B3-1
IQCN	ENST00000600359.7 linkuse as main transcript	c.2862C>A	p.His954Gln	missense_variant	4/4	2		ENSP00000472912.1	Q9H0B3-5
IQCN	ENST00000599638.2 linkuse as main transcript	n.4896C>A		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.000559

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000168

AC:

AN:

244344

Hom.:

AF XY:

0.000105

AC XY:

AN XY:

133654

show subpopulations

Gnomad AFR exome

AF:

0.00258

Gnomad AMR exome

AF:

0.0000582

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000528

AC:

AN:

1458070

Hom.:

Cov.:

AF XY:

0.0000414

AC XY:

AN XY:

724996

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.0000897

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000233

GnomAD4 genome

AF:

0.000591

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00209

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000281

Hom.:

Bravo

AF:

0.000574

ESP6500AA

AF:

0.00162

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000199

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 24, 2023

The c.3561C>A (p.H1187Q) alteration is located in exon 4 (coding exon 3) of the KIAA1683 gene. This alteration results from a C to A substitution at nucleotide position 3561, causing the histidine (H) at amino acid position 1187 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.48

DANN

Benign

0.71

DEOGEN2

Benign

0.0019

T;T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.30

T;T;T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-0.89

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.2

.;.;.;N

REVEL

Benign

0.012

Sift

Benign

0.36

.;.;.;T

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.012

.;B;.;.

Vest4

0.087

MutPred

0.30

.;Gain of MoRF binding (P = 0.0893);.;.;

MVP

0.085

MPC

0.18

ClinPred

0.011

GERP RS

-4.4

Varity_R

0.039

gMVP

0.093

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over